generating mucosal immunity after influenza infection and vaccination in lung and lymphoid tissue

Conditions: Influenza

Summary: this experimental medicine study aims to compare immune responses in healthy adult volunteers aged 18-40 years against influenza vaccination and infection in the upper and lower respiratory tract, following administration of a live-attenuated influenza vaccine delivered by nasal spray versus influenza a (h3n2) viral challenge.


Eligibility criteria:
inclusion criteria: * adults aged between 18-40 years inclusive * sero-suitable as defined by a serum micro-neutralisation titre \<1:20 * female participant who is not of child-bearing potential as assessed by an investigator or is willing and able to use contraception as described in the protocol * male participants who are willing to use one of the contraception methods described in the protocol * in good health with no clinically significant medical conditions exclusion criteria * history of clinically significant/currently active conditions; * cardiovascular, thromboembolic/cerebrovascular disease. * types of chronic respiratory disease in adulthood. * significant wheeze in the past * respiratory symptoms including wheeze, resulting in hospitalisation * known bronchial hyperactivity to viruses * diabetes mellitus * migraine with associated symptoms like hemiplegia/vision loss. cluster headache/migraine/prophylactic treatment for migraine. * history of autoimmune disease/known immunodeficiency of any cause * immunosuppression. * known coagulation disorder/anticoagulant therapy * psychiatric illness including participants with a history of depression and/or anxiety with associated psychiatric comorbidities * other major disease that, under the pi's discretion, could interfere with the participant completing the study. * concurrent serious illness including history of malignancy that could interfere with the study or a participant completing the study. * known iga deficiency/immotile cilia syndrome/kartagener's syndrome * significant abnormality altering the anatomy/function of the nose or nasopharynx, a clinically significant history of epistaxis within the last 3 months, nasal/sinus surgery within 6 months of day 0, including nasopharyngeal malignancy, arterio-venous malformation, or undiagnosed nasopharyngeal mass * inhaled bronchodilator/inhaled steroid use within the last 12 months before day 0 * acute upper respiratory tract infection in the past 6 weeks. * receipt of systemic glucocorticoids (in a dose ≥ 5 mg prednisone daily or equivalent) within one month, or any other cytotoxic or immunosuppressive drug within 6 months before day 0 * receipt of any vaccine within 30 days of day -14 * any significant medical condition/prescribed drug, under the pi's discretion * presence of cold-like symptoms and/or fever on day -14 or day 0. * receipt of blood/blood products/loss (including blood donations) of 550 ml or more of blood during the 3 months prior to day -14. * significant history/presence of drug/alcohol misuse by self-report. * current use of drugs through nose inhalation or inhaled route including recreational drugs. * regular smoking and/or vaping and/or using nicotine-containing products in the past 3 months or \>5 pack-year lifetime history by self-report (5 pack years is equivalent to one pack of 20 cigarettes per day for 5 years). * history of anaphylaxis and/or a history of severe allergic reaction or significant intolerance to any food/drug, as assessed by the pi. * clinically active rhinitis (including hay fever)/history of moderate to severe rhinitis/history of seasonal allergic rhinitis likely to be active at the time of inclusion into the study and/or requiring regular nasal corticosteroids on an at least weekly basis, within 30 days of enrolment. * anyone with any of the following contraindications to receiving the fluenz tetra vaccine: * allergy to gentamicin, gelatin or the other ingredients of the fluenz vaccine.

Keywords: laiv challenge vaccine influenza flu